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Ann Thorac Surg 1997;63:1361-1367
© 1997 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Endothelin-1 and Neutrophil Activation During Heparin-Coated Cardiopulmonary Bypass

Department of Cardiothoracic Surgery, Ullevaal Hospital, Oslo, Norway

Accepted for publication December 6, 1996.

	Abstract

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 
Background. Heparin-coated circuits attenuate the systemic inflammatory response to cardiopulmonary bypass. The present study compares two different heparin coatings in terms of the release of endothelin-1 and neutrophil glycoproteins.

Methods. Forty low-risk patients undergoing coronary artery bypass grafting were investigated, having cardiopulmonary bypass with a Duraflo II heparin-coated circuit (n = 10), an identical but uncoated circuit (n = 10), a Carmeda BioActive Surface heparin-coated circuit (n = 10), or an identical but uncoated circuit (n = 10). A standard systemic heparin dosage was used in all patients. Endothelin-1 and the neutrophil glycoproteins lactoferrin and myeloperoxidase were quantified throughout the operation and 3 hours postoperatively.

Results. Enhanced plasma levels of endothelin-1, lactoferrin, and myeloperoxidase were observed during and after uncoated cardiopulmonary bypass, but this was not associated with clinical side effects. Compared with the respective uncoated controls, Duraflo II attenuated only the lactoferrin levels, whereas Carmeda BioActive Surface was associated with lower levels of both endothelin-1, lactoferrin, and myeloperoxidase. Of the two heparin coatings, Carmeda BioActive Surface proved more effective than Duraflo II in attenuating the levels of these substances.

Conclusions. The plasma levels of endothelin-1, lactoferrin, and myeloperoxidase increase during cardiopulmonary bypass in coronary artery bypass grafting, but this has no clinical side effects in low-risk patients. The increase is attenuated using heparin-coated extracorporeal circuits, and then more effectively by Carmeda BioActive Surface than by Duraflo II.

	Introduction

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 
During cardiopulmonary bypass (CPB), the interaction between blood and the synthetic surface of the extracorporeal circuit activates cascade systems and blood cells to produce a variety of substances that mediate a systemic inflammatory response. Usually, this reaction passes subclinically, but it may occasionally progress to end-organ failure. The use of heparin-coated circuits significantly reduces the activation of the complement system and blood cells, denoted as improved biocompatibility [1–3].

Endothelin-1 is the most powerful vasoconstrictor yet identified in the human organism. High plasma concentrations are observed during open heart operations, myocardial infarction, ischemia, renal failure, sepsis, preeclampsia, and major surgical procedures, and it is suggested that endothelin-1 can mediate cardiac failure, vasoconstriction, and tissue hypoperfusion in at least some of these disorders [4]. Cardiopulmonary bypass initiates physiologic changes, which each can induce endothelin-1 synthesis. These include: hypoxia, shear-stress, and release of thrombin, endotoxin, tumor necrosis factor, interleukin-1, interleukin-6, and interleukin-8. It has recently been demonstrated that the use of heparin-coated CPB can attenuate at least some of these endothelin-1 inducers [5].

The aim of this study was to examine the plasma levels of endothelin-1 and the neutrophil glycoproteins lactoferrin and myeloperoxidase during coronary artery bypass grafting using two different heparin-coated extracorporeal circuits, Carmeda BioActive Surface (CBAS) and Duraflo II.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 
Patients
Patients undergoing coronary artery bypass grafting without any additional procedures were included in the study. Some of the clinical results and neutrophil glycoprotein data are previously published [6]. The exclusion criteria were known coagulopathy, ongoing anticoagulation or antiinflammatory therapy, respiratory, hepatic, or renal failure, and ejection fraction less than 0.40. No patients received aprotinin. Forty patients were randomly assigned to CPB in one of four groups: Duraflo II heparin coated (n = 10), Duraflo II uncoated control (n = 10), CBAS heparin coated (n = 10), and CBAS uncoated control (n = 10).

	DURAFLO II GROUP.

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 
The circuit (Baxter-Bentley Laboratories, Irvine, CA) consisted of polyvinyl chloride tubings connected to a hard-shell cardiotomy reservoir (BCR-3500), a soft-shell venous reservoir (BMR-1900), a woven hollow-fiber membrane oxygenator (Univox), a 25-µm artery line filter (AF-1025), and a prebypass filter (RP-10). The entire blood contact surface was coated with a ionic-bonded, unfragmented and water-insoluble heparin complex, using the Duraflo II method (Baxter-Bentley).

	DURAFLO II CONTROL GROUP.

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 
The extracorporeal circuit was uncoated, but otherwise identical to the Duraflo II coated equipment.

	CBAS GROUP.

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 
The circuit (Medtronic, Anaheim, CA) consisted of polyvinyl chloride tubings connected to a hard-shell cardiotomy reservoir (Intersept 2500), a soft-shell venous reservoir (MVR 1600), a woven hollow-fiber membrane oxygenator (Maxima), a 40-µm artery line filter (Intersept 40), and a prebypass filter (Intersept PBP). The entire blood contact surface was coated with endpoint-attached covalent-bonded fragmented heparin, using the CBAS method (Medtronic).

	CBAS CONTROL GROUP.

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 
The extracorporeal circuit was uncoated but otherwise identical to the CBAS coated equipment.

	Anesthesia, Cardiopulmonary Bypass, and Operation

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 
For the anesthesia, thiopental sodium, diazepam, fentanyl, pancuronium, and nitrous oxide were used in a standard combination. For all operations, a nonpulsatile roller pump (Gambro, Horten, Norway) was used, and the extracorporeal circuit was primed with 2,000 mL of Ringer's acetate. Heparin, 400 IU/kg body weight (Leo, Ballerup, Denmark), was administered intravenously before the onset of CPB, and the activated coagulation time had to be at least 480 seconds before CPB was started. The operations were performed under moderate general hypothermia (28° to 32°C), using topical ice slush cooling and antegrade cold St. Thomas' Hospital no. 2 cardioplegic solution. Autologous blood was removed before CPB and subsequently retransfused. Cardiotomy reservoirs were used in all operations. All contents of the extracorporeal circuit was returned to the patient, and shed mediastinal blood was autotransfused until 18 hours after the operation. The bolus of protamine sulfate (Leo) was administered in a dosage equal to that of heparin. If necessary, additional protamine was given to reestablish the preoperative activated coagulation time level. The amount of heparin and protamine administered, the duration of operation, CPB, and aortic occlusion, and the postoperative blood loss from the two mediastinal drains were recorded in all patients.

The distal anastomoses were performed with the aorta cross-clamped, whereas the proximal anastomoses were sutured using partial occlusion of the ascending aorta during rewarming. The ventilation of the lungs was terminated when CPB was started, and reinstituted a few minutes before conclusion of CPB.

	Blood Samples and Analyses

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 
Blood was collected in ethylenediaminetetraacetic acid tubes at the following intervals: (1) after induction of anesthesia, (2) at the onset of CPB, (3) 10 minutes after decamping of aorta, and (4) 3 hours postoperatively. All samples were kept on melting ice and centrifuged at 2,000 g within 3 hours, and the plasma was stored at -70°C. The concentrations of endothelin-1, lactoferrin, and myeloperoxidase were corrected for hemodilution during CPB. The percent change in plasma volume from hemoglobin change was yielded by the following formula: [100/(100 - initial hemoglobin)] x [100 x (initial hemoglobin - sample hemoglobin)/sample hemoglobin] [7].

ENDOTHELIN-1 ENZYME-LINKED IMMUNOSORBENT ASSAY.
Plasma endothelin-1 was measured with the Biotrak Endothelin-1 enzyme-linked immunosorbent assay system (Amersham, Bucks, UK). Endothelin-1 was extracted from the plasma in 500 mg C2 columns (Amprep RPN 1913; Amersham). The columns were equilibrated by washing with 2 mL of methanol followed by 2 mL of water. A 1-mL sample of plasma was acidified with 0.25 mL of 2 mol/L hydrogen chloride to improve recovery and then centrifuged at 10,000 g for 5 minutes at room temperature to remove the larger polypeptides. The supernatant was loaded into the column and then washed with 5 mL of water with 0.1% trifluoroacetic acid. The column was eluated with 2 mL of 80% acetonitrile in water with 0.1% trifluoroacetic acid. The eluent was collected in glass tubes, dried under nitrogen gas for 1 hour until the residual volume was 1 mL, and then evaporated to dryness at -70°C. The sample was resuspended in 250 µL assay buffer, from which 100 µL was used for analysis. The Biotrak Endothelin-1 ELISA recognizes 21 amino acid endothelin-1 (cross-reactivity, 100%) and endothelin-2 (cross-reactivity, >100%), but not endothelin-3 or big endothelin. The sensitivity is 6 pg/mL.

NEUTROPHIL GLYCOPROTEINS.
Lactoferrin and myeloperoxidase in plasma were quantified using radioimmunoassays (Kabi Pharmacia Diagnostica, Sweden) as previously described [8].

	Statistics

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 
Data are presented as mean values and standard errors of mean. The Friedman test was used for analysis of time-dependent changes within each group, and longitudinal changes between two time points only were analyzed with the Wilcoxon signed rank test. Comparisons between groups at each time point were not considered relevant, as the sample points were related to the progress of the operation and therefore, differed in each patient [9]. Instead, in each patient, the maximal value and the sum of values after onset of CPB were registered, and the mean values for these parameters in each group were compared with the Kruskal-Wallis and Mann-Whitney tests. Correlation analyses were performed using the Spearman rank test. A p value less than 0.05 was considered statistically significant.

	Results

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 
Clinical Data
Ninety percent of the 40 patients enrolled in the study were men. There were no significant differences between the groups in age distribution, male to female ratio, number of distal anastomoses, CPB time, cross-clamp time, activated coagulation time, amounts of administered heparin and protamine, postoperative mediastinal blood drainage, or retransfusion volumes (Table 1).

	Endothelin-1

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

View larger version (27K): [in this window] [in a new window]   Fig 1. . Plasma levels of endothelin-1 (mean ± standard error of the mean) in coronary artery bypass grafting using cardiopulmonary bypass (CPB) with Carmeda BioActive Surface (CBAS) or Duraflo II heparin-coated and respective uncoated control circuits.

View larger version (24K): [in this window] [in a new window]   Fig 2. . Maximal values and the sum of generated amount of plasma endothelin-1, lactoferrin, and myeloperoxidase (mean ± standard error of the mean) in patients undergoing coronary artery bypass grafting using cardiopulmonary bypass with Carmeda BioActive Surface (CBAS) or Duraflo II heparin-coated and respective uncoated control circuits. (*p < 0.05 versus the respective uncoated control; p < 0.05 versus Duraflo II; Kruskal-Wallis and Mann-Whitney tests.)

	Neutrophil Glycoproteins

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

	Comment

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

The inflammatory response to CPB involves activation of cascade systems and the stimulation of endothelial cells, monocytes, neutrophils, and endocrine organs, with the subsequent release of a variety of vasoactive and inflammatory mediators. The endothelium is the source of both vasodilators (nitric oxide and prostacyclin) and vasoconstrictors (endothelin-1). These factors show a complex interplay, as nitric oxide and prostacyclin suppress endothelin-1 release, whereas endothelin-1 stimulates synthesis of nitric oxide by the endothelial endothelin-B receptor. Endothelin-1 is released into the systemic circulation during CPB and major surgical procedures [10, 11]. Renin, vasopressin, angiotensin II, catecholamines, thrombin, endotoxin, tumor necrosis factor, and interleukins are released during CPB, and these substances have the potential to stimulate endothelin-1 synthesis. Other factors like surgical stress, shear stress, vascular injury, and hypoxia may also contribute to endothelin-1 release during open heart operations. The synthesis of endothelin-1 is regulated at the transcriptional level, because endothelial cells have no intracellular stores of endothelin-1 [12]. The half-time of endothelin-1 in the circulation is about 1 minute; therefore, the plasma level at a given point of time reflects the sum of synthesis and degradation within a period of few minutes. In the present study, the plasma endothelin-1 level did not increase until the start of CPB, and this phenomenon is in accordance with previous reports in cardiac operations [10]. Although a major surgical procedure itself can stimulate release of catecholamines and other vasoactive substances [10], the lack of endothelin-1 release in the pre-CPB phase may be attributable to the fact that the sternotomy and the cannulation involve only minor surgical stress or that the endothelin-1 response is delayed because of peptide de novo synthesis. The plasma levels of endothelin-1 during CPB have been shown to correlate to high age and perioperative oxygen consumption, but not to catecholamine levels, hemodynamic performance, or cutaneous laser Doppler flow parameters [10]. In the present study, the plasma endothelin-1 remained elevated in the postoperative phase, which accords well with the fact that endothelin-1-inducing substances continue to be released after the operative procedure. Principally, enhanced plasma levels of endothelin-1 may be due to increased synthesis or reduced clearance. Endothelin-1 is removed from the circulation mainly in the lungs and kidneys. During CPB, the pulmonary clearance is inherently reduced, and this could, at least partly, explain the rise in endothelin-1 during extracorporeal circulation. However, there are at least two arguments against such a mechanism. First, plasma endothelin-1 continued to increase after the end of CPB, when the pulmonary clearance should be intact. Second, in the CBAS-coated group there was no increase in plasma endothelin-1 during CBP. This indicates that the rise in plasma endothelin-1 is not a result of reduced clearance, but rather a consequence of increased endothelin-1 synthesis attributable to an inflammatory reaction. Larger plasma proteins like albumin and fibrinogen are absorbed to the heparin-coated surface of the circuit, whereas smaller peptides like endothelin-1 and neutrophil glycoproteins are less likely to bind to the synthetic surface. Nevertheless, this absorbance phenomenon cannot be the sole explanation to the CBAS-induced attenuation of endothelin-1 and neutrophil glycoproteins. This is because CBAS was associated with lower levels of endothelin-1 and neutrophil glycoproteins, not only during CPB, but also in the postoperative phase, strongly suggesting that this coating improves the biocompatibility of the extracorporeal circuit and reduces the CPB-induced whole-body inflammation [1–3].

The effect of postoperative retransfusion on the plasma levels of endothelin-1, lactoferrin, and myeloperoxidase is not fully understood. Probably due to activation of the extravasated blood, substances originating from plasma cascade proteins (complement and fibrin) and from leukocytes (cytokines and neutrophil glycoproteins) are compartmentalized in the shed mediastinal blood. Therefore, postoperative autotransfusion may tend to sustain or increase the plasma levels of these substances, and subsequently stimulate endothelin-1 synthesis. The endothelium is the main source of endothelin-1, but it is also produced in monocytes/macrophages. Theoretically, endothelin-1 should be less compartmentalized in the shed mediastinal blood than those substances originating from the blood itself, but this remains to be studied.

Activated neutrophils release proteolytic enzymes, free oxygen radicals, and other inflammatory mediators of significant importance in the development of end-organ dysfunction. Several granulocyte-activating substances are released during CPB; these include endotoxin, tumor necrosis factor, interleukins, endothelin-1, and activated complement, especially C5a. Within the neutrophils, lactoferrin is stored in the specific cytoplasmic granules and myeloperoxidase in the azurophilic granules. Enhanced levels of lactoferrin and myeloperoxidase have previously been reported in the setting of in vitro and in vivo CPB. In the present study, the lactoferrin and myeloperoxidase values increased significantly from baseline in both the uncoated control groups. This rise was prevented by CBAS coating, but not by Duraflo II coating. CBAS proved more effective than Duraflo II in attenuating the levels of lactoferrin (maximal values and sum of generated amount) and myeloperoxidase (sum of generated amount), indicating lower neutrophil activation during CPB. Although the most obvious explanation of this difference is the dissimilar heparin coating processes-covalent-bonded endpoint-attached fragmented heparin (CBAS) versus ionic-bonded unfragmented heparin (Duraflo II), one cannot exclude the possibility that the oxygenator difference-Maxima versus Univox-can explain some of the observed differences regarding the release of endothelin-1 and neutrophil glycoproteins.

The release of endothelin-1, lactoferrin, and myeloperoxidase during CPB is most likely a part of the whole-body inflammation, and lower levels of these substances using heparin-coated circuits thus reflects the attenuation of the inflammatory response. In the present study, heparin coating was associated with reduced levels of both endothelin-1 and lactoferrin, and to some degree myeloperoxidase. Although this mutual reduction may be due to attenuation of common inducers, it can also be attributed to a more direct interplay between neutrophil activation and endothelin-1 release. In fact, endothelin-1 has been shown to increase neutrophil adhesion to endothelial cells by inducing CD11/CD18 expression [13]. Moreover, neutrophils convert exogenously supplied big endothelin-1 into mature endothelin-1, probably by the action of one or more metalloproteases [14].

In low-risk patients, coronary artery bypass grafting is a safe procedure, and a moderate release of endothelin-1 and neutrophil glycoproteins does not predict increased morbidity or mortality. However, the clinical significance of these biochemical changes remains to be explored in more complex heart operations and in patients with high-risk operative profiles. At the present, no reports exist that correlate enhanced plasma concentration of endothelin-1 to poor clinical outcome in open heart operations, but such a connection has been reported in other major pathophysiologic conditions like sepsis [15] and renal failure [16, 17]. Excessive endothelin-1 release has potential deleterious effects on the postoperative course in cardiac operations. Endothelin-1 has positive chronotropic and inotropic effects on isolated myocytes, but due to a simultaneous coronary and systemic vasoconstriction the net in vivo effect is reduced cardiac output. Endothelin-1 and nitric oxide are opposing paracrine mediators produced and acting in the coronary vasculature. Recent reports suggest that after hypothermic ischemia and reperfusion of the heart, there is reduced nitric oxide production, but continued or enhanced endothelin-1 production, resulting in a vasoconstrictory dominance. Accordingly, exogenously supplied L-arginine, the precursor of nitric oxide, offsets the detrimental effect of endothelin-1 and results in recovery of coronary blood flow and left ventricular function in the postischemic heart [18]. Individual vascular beds differ widely in their responsiveness to endothelin-1; the renal vasculature being the most sensitive. Because the renal vessels are more sensitive than the coronary vasculature, a moderate release of endothelin-1 may provoke renal hypoperfusion without affecting cardiac performance.

Conduits used in coronary artery bypass grafting have different sensitivity to endothelin-1. Veins are usually more sensitive than their accompanying arteries, which has been demonstrated for both the saphenous and internal mammary vessels [19, 20], and the constriction is mediated by both endothelin-A and endothelin-B receptors in the smooth muscle cells [21–23]. Contractile effects of endothelin-1 have been described for the gastroepiploic artery, the inferior epigastric artery, and for the internal mammary artery [19, 24–26]. The endothelin-1-induced contractility is approximately the same in the inferior epigastric artery and the internal mammary artery [25], whereas the gastroepiploic artery, having a predominantly muscular media, contracts to higher forces [24]. The endothelium of the internal mammary artery does not express functional endothelin-B receptors linked to nitric oxide and/or prostacyclin production [27], which can explain why endothelin-1 gives no transitory dilation in this artery and why removal of the endothelium does not affect endothelin-1-induced vasospasm of the human internal mammary artery [28]. Histologic studies have suggested that the human internal mammary artery is an elastic, passive conduit along the majority of its length, and that vasospams mainly take place in the distal muscular part. Although the distal part is the most reactive part of the graft, also the middle and proximal portion contracts in response to endothelin-1 and should therefore not be regarded as just passive segments of the internal mammary artery [29, 30]. Of clinical importance, an internal mammary artery that is contracted by endothelin-1 relaxes significantly in response to both glyceryl nitrate and calcium antagonists [31, 32]. Independent of the conduit in use, it is obvious that endothelin-1 may profoundly affect the contractile state of the coronary graft, and excessive release of endothelin-1 may thus have the potential to provoke spasm and subsequently thrombosis of the graft.

In conclusion, the plasma levels of endothelin-1, lactoferrin, and myeloperoxidase increase in open heart operations, especially during CPB, but this has no clinical side effects in low-risk patients.The response is attenuated by heparin coating of the extracorporeal circuit, and then more effectively by CBAS than by Duraflo II.

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 
We thank Per Ekstroem, BS, for assistance with the analysis of endothelin-1.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 
Address reprint requests to Dr Lundblad, Department of Cardiothoracic Surgery, Ullevaal Hospital, N-0407 Oslo, Norway.

	References

Top Footnotes Abstract Introduction Material and Methods DURAFLO II GROUP. DURAFLO II CONTROL GROUP. CBAS GROUP. CBAS CONTROL GROUP. Anesthesia, Cardiopulmonary... Blood Samples and Analyses Statistics Results Endothelin-1 Neutrophil Glycoproteins Comment Acknowledgments References

 

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